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1.

Background:

Serologic screening of gastric cancer (GC) by serum pepsinogens (sPG) levels and Helicobacter pylori (Hp) sero-status, though highly informative, has provided heterogeneous results. Here, we have evaluated the modifying effects of demographic factors on the risk impact of Hp sero-status/sPG levels in gastric cancer, with particular emphasis on age.

Methods:

A cross-sectional study was carried out on 1341 individuals (GC = 578, healthy = 763), who were stratified into two age groups: 35-59 years (middle-aged, n = 830) and ≥ 60 years (60 years-plus, n = 511). Demographic factors and serological states (Hp sero-staus and sPG levels) were recorded by subject interview and serum ELISAs, respectively. Covariate-specific odds ratios were calculated by multivariable logistic regression.

Results:

Hp infection was consistently associated with increased sPGI and sPGII levels in the 60 year-plus, but not the middle-aged group. The joint examination of the variable states of the three serum biomarkers (Hp serology, sPGI, and sPGI/II ratio), in the 60 year-plus age group, demonstrated a stepwise escalation of risk from the single (sPGIlow; OR = 2.6), to double (sPGIlow/sPGI/IIlow; OR = 3.55, and Hppositive/sPGIlow; OR = 5.0) and ultimately triple (Hppositive/PGIlow/PGI/IIlow; OR = 10.48) positive states, in reference to the triple negatives. However, this pattern was not exhibited in the middle-aged subjects.

Conclusion:

Age was clearly identified as a modifying factor on the risk projection of the combined states of Hp serology and sPG levels in gastric cancer screening, reflected by the augmented (~10.5 fold) risk of GC in the triple positive (Hppositive/sPGIlow/sPGI/IIlow) 60 year-plus subjects, which was not evident in the middle-aged group. Key Words: Biomarkers, Demography, Age Distribution  相似文献   

2.
Background:Methadone therapy is a major protocol in opioid addiction cases in many health care systems. Population-based studies have shown that in addicted people, the genetic profile affects their response to methadone therapy. Therefore, this study designed to examine the frequency of two SNPs of the CYP2B6 gene (rs3745274 and rs3211371) in addicted cases in two methadone-responders and methadone non-responders groups. Methods:A total of 199 opioid-addicted individuals and 117 unaffected control subjects were genotyped for rs3745274 and rs3211371 polymorphisms of the CYP2B6 gene using the tetra-primer ARMS-PCR. Results:Results of this study revealed the significant association of rs3745274 GG (p < 0.001; OR = 0.027; 95% CI = 0.14-0.49) and GT (p < 0.001; OR = 4.04; 95% CI = 2.26-7.21) genotypes with the risk of addiction in methadone-responders. Also, a significant association between rs3745274 GG (p < 0.001; OR = 0.28; 95% CI = 0.15-0.51) and GT (p < 0.001; OR = 5.1; 95% CI = 2.8-5.28) genotypes and addiction relapse was found in methadone non-responders. Conclusion:Based on our findings, we can conclude that rs3745274 variant of CYP2B6 gene could serve as a potential biomarker, to evaluate the prognosis of addicted people fate under treatment with methadone. Key Words: Addiction, Biomarker, Methadone, Single-nucleotide polymorphism  相似文献   

3.
4.
Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease with many genetic factors predisposing to disease susceptibility. The aim of the present study was to investigate the impact of CD226 rs727088 and rs763361 polymorphisms and susceptibility to RA in a sample of the Iranian population. Methods: This case-control study was carried out on 100 patients with RA and 104 healthy subjects. The polymorphisms were determined using tetra amplification refractory mutation system-polymerase chain reaction assay. Results: The rs763361 (Gly307Ser) polymorphism increased the risk of RA in codominant, dominant and recessive-tested inheritance models (odds ratio [OR] = 3.18, 95% confidence intervals [95% CI] = 1.44-7.02, P = 0.004, CC vs. TT, and OR = 1.98, 95% CI = 1.10-3.57, P = 0.023, CC vs. CT-TT, and OR = 2.61, 95% CI = 1.26-5.37, P = 0.010, CC + CT vs. TT, respectively). In addition, the rs763361 T allele increased the risk of RA (OR = 2.06, 95% CI = 1.38-3.08, P<0.001). However, no significant difference was observed among the groups regarding CD226 rs727088 polymorphism (χ2 = 3.20, P = 0.202). Conclusions: Our finding showed that CD226 rs763361, but not rs727088, gene polymorphism increased the risk of RA in a sample of the Iranian population.Key Words: Rheumatoid arthritis (RA), CD226, Polymorphism  相似文献   

5.
Background:IM, a strong and selective TKI, has been approved as the front line of treatment in CML patients. In spite of satisfactory results of imatinib in the treatment of patients with CML, patients with treatment failure or suboptimal response developed resistance that might be because of pharmacogenetic variants. This study attempted to evaluate the influence of ABCB1 gene polymorphisms and smoking on CML risk and resistance to imatinib. Methods: ABCB1 (c.1236C>T, c.3435C>T) polymorphisms were genotyped in 98 CML patients and 100 sex- and age-matched healthy subjects by PCR-RFLP method, followed by sequencing. The patients were evaluated for cytogenetic response by the standard chromosome banding analysis in regular intervals. Results:Our results showed that c.1236CC genotype was significantly associated with imatinib resistance (OR = 3.94; p = 0.038). Analysis of the joint of SNP-smoking combination showed that smokers with c.1236TT/CT and c.1236CC genotypes had the increased risk of CML (OR = 6.04; p = 0.00 and OR = 4.95, p = 0.005) and treatment failure (OR = 5.36, p = 0.001 and OR = 15.7, p = 0.002), respectively. Smokers with c.3435TT/CT and c.3435CC genotypes also displayed the elevated risk of CML development (OR = 6.01, p = 0 and OR = 4.36, p = 0.011) and IM resistance (OR = 5.61, p = 0.001 and OR = 13.58, p = 0.002), respectively. Conclusion:Our findings suggest that c.1236CC genotype has clinical importance in the prediction of treatment outcome with IM, and smoking could have a synergistic role in CML risk and IM resistance. Key Words: ATP binding cassette transporter subfamily B, Imatinib mesylate, Smoking  相似文献   

6.

Background

Attempts for early detection of gastric cancer have recently focused on host''s genetic susceptibility factors and gene-environment interactions. We have, herein, studied the association of MTHFR C677T single nucleotide polymorphism (SNP) and its interaction with Helicobacter pylori infection, smoking, age and gender on the risk of gastric cancer among an Iranian population.

Methods

Gastric cancer patients (n = 450) and cancer-free controls (n = 780) were studied for serum H. pylori-specific IgG antibodies by ELISA and MTHFR C677T polymorphism (SNP) by PCR-RFLP. Demographic and life style data were collected through patient interviews. Unconditional logistic regression model estimated odds ratio (OR) and the corresponding 95% confidence intervals (CI).

Results

The interactions of MTHFR genotype with H. pylori infection (P = 0.03), age (P = 0.049) and gender (P = 0.007) were statistically significant. Accordingly, MTHFR C677T carriers who were also positive for H. pylori infection exhibited 80% (OR = 1.8, 95% CI = 1.0-2.9) significant excess risk of non-cardia gastric cancer. Furthermore, subjects over the age of 50 or female subjects carrying MTHFR C677T SNP showed 40 (OR = 1.4, 95% CI = 1.0-2.0) and 100 (OR = 2.0, 95% CI = 1.2-3.2) percent increased risk of gastric cancer, respectively.

Conclusion

MTHFR C677T SNP seems to increase the risk of gastric cancer and the effect is significantly inflated by interactions with H. pylori infection, age and gender. Key Words: Helicobacter pylori, Smoking, Gender identity, Age group, Methylenetetrahydrofolate reductase  相似文献   

7.
8.
Background: MDM2 (Murine Double Minute2) is an oncoprotein that inhibits the P53 activity. Overexpression of MDM2 gene has been reported in several human tumors. In the present study, we aimed to evaluate the impact of 40-bp insertion/deletion (ins/del) polymorphism on the promoter of MDM2 and susceptibility to breast cancer in a sample of Iranian population. Methods: This case-control study was carried out on 236 patients with breast cancer and 203 healthy individuals. Genomic DNA was extracted from the whole blood by the salting-out method. The 40-bp ins/del polymorphism was determined by using polymerase chain reaction. Results: The findings indicated that MDM2 ins/del variant increased the risk of breast cancer in co-dominant- (odds ratio [OR] = 2.09, 95% CI = 1.14-3.85, P = 0.018, del/del vs. ins/ins), dominant- (OR = 1.49, 95% CI = 1.02-2.18, P = 0.038, ins/del + del/del vs. ins/ins), and recessive- (OR = 1.86, 95% CI = 1.03-3.34, P = 0.038, del/del vs. ins/ins + ins/del) tested inheritance models. The del allele increased the risk of breast cancer (OR = 1.48, 95% CI = 1.11-1.98, P = 0.008) compared with ins allele. Conclusions: Our result revealed that 40-bp ins/del polymorphism in the promoter of MDM2 increased the risk of breast cancer in an Iranian population. Further investigations with larger sample sizes and diverse ethnicities are needed to verify our findings. Key Words: Breast cancer, Murine Double Minute2 (MDM2), Polymorphism  相似文献   

9.
Background:LINC-ROR, as a cancer-related lncRNA, has vital roles in stem cell survival, pluripotency, differentiation, and self-renewal in hESCs. However, cancer-related molecular mechanisms, its functional roles, and clinical value of LINC-ROR in GC remain unclear. In this study, we aimed to investigate probable interplay between LINC-ROR with SALL4 stemness regulator and their role with the development of the disease. Methods:The mRNA expression profile of LINC-ROR and SALL4 was assessed in tumoral and adjacent non-cancerous tissues of GC patients, using quantitative real-time PCR. Results:Significant LINC-ROR underexpression and SALL4 overexpression were observed in 55.81% and 75.58% (p < 0.0001) of samples, respectively. The expression of LINC-ROR and SALL4 were significantly correlated with each other (p = 0.044). There was an association between the underexpression of LINC-ROR and sex, stage of tumor progression, tumor type, and location of tumor (p < 0.05), and H. pylori infection with SALL4 expression (p = 0.036). There were also significant correlations between concomitant mRNA expression of SALL4 and LINC-ROR in tumors located at distal noncardiac, positive for H. pylori infection, tumors with invasion into the muscle layer of the stomach, and grade II tumor (p < 0.05). Conclusion:The clinical results of the SALL4-LINC-ROR association propose a probable functional interaction between these markers in tumor maintenance and aggressiveness. Our study can help to understand one of the mechanisms involved in the progression of GC through the function of these regulators. Key Words: LINC-ROR, Non-coding RNA, SALL4  相似文献   

10.

Background

The aim of this study was to understand any association between differentiated thyroid carcinoma (DTC) and Ile3434Thr XRCC7 gene polymorphism (GenBank accession number: rs7830743). DTC is the most prevalent thyroid neoplasm, which includes papillary and follicular cell carcinoma. XRCC7 gene encodes a protein that functions in non-homologous end joining DNA repair pathway. Non-synonymous polymorphisms in this gene may alter DNA repair capacity of the cell and change the risk of developing cancers.

Methods

DTC patients (n = 173) and cancer free individuals (n = 204) were enrolled in a case-control study. The Ile3434Thr polymorphic alleles were discriminated by using amplification refractory mutation system-PCR method. The frequencies of this single nucleotide polymorphism in case and control groups were compared. Also, risk ratio for developing DTC in dichotomized genotypes was estimated by multivariate logistic regression analysis.

Results

Dichotomized genotypes into those with and without the 3434Thr allele showed that this allele was associated with DTC (OR [odd ratio]: 1.89, 95% confidence interval (CI) = 1.29-2.79, P<0.001). Also, TC genotype was significantly associated with increased risk of DTC (OR: 2.42, 95% CI = 1.55-3.81, P = 0.0001) in individuals carrying this genotype.

Conclusion

Allele 3434Thr in XRCC7 gene might be associated with differentiated thyroid cancer risk. Further studies with larger samples are needed to verify these initial findings. Key Words: DNA repair enzymes, Thyroid neoplasms, Genetic polymorphism  相似文献   

11.
The present case-control study explored the interaction between marine-derived n-3 long chain polyunsaturated fatty acids (n-3 LC PUFAs) and uric acid (UA) on glucose metabolism and risk of type 2 diabetes mellitus (T2DM). Two hundred and eleven healthy subjects in control group and 268 T2DM subjects in case group were included. Plasma phospholipid (PL) fatty acids and biochemical parameters were detected by standard methods. Plasma PL C22:6n-3 was significantly lower in case group than in control group, and was negatively correlated with fasting glucose (r = −0.177, p < 0.001). Higher plasma PL C22:6n-3 was associated with lower risk of T2DM, and the OR was 0.32 (95% confidence interval (CI), 0.12 to 0.80; p = 0.016) for per unit increase of C22:6n-3. UA was significantly lower in case group than in control group. UA was positively correlated with fasting glucose in healthy subjects, but this correlation became negative in T2DM subjects. A significant interaction was observed between C22:6n-3 and UA on fasting glucose (p for interaction = 0.005): the lowering effect of C22:6n-3 was only significant in subjects with a lower level of UA. In conclusion, C22:6n-3 interacts with UA to modulate glucose metabolism.  相似文献   

12.
Background: Glaucomatous neuropathy is a type of cell death due to apoptosis. The p53 gene is one of the regulatory genes of apoptosis. Recently, the association between the p53 gene encoding for proline at codon 72 and primary open-angle glaucoma (POAG) has been studied in some ethnic groups. This study is the first association analysis of POAG and p53 codon 72 polymorphism in Iranian patients. Methods: A cohort of 65 unrelated patients with POAG (age range from 12-62 years, mean ± SD of 40.16 ± 17.51 years) and 65 unrelated control subjects (without glaucoma, age range of 14-63 years, mean ± SD of 35.64 ± 13.61 years) were selected. In Iranian POAG patients and normal healthy controls, the p53 codon 72 polymorphism in exon 4 was amplified using polymerase chain reaction. The amplified DNA fragments were digested with the BstUI restriction enzyme, and the digestion patterns were used to identify the alleles for the polymorphic site. Results: Comparisons revealed significant differences in allele and genotype frequencies of Pro72Arg between POAG patients and control group. A higher risk of POAG was associated with allele Pro (OR = 2.1, 95% CI = 1.2–3.4) and genotype Pro/Pro (OR = 3.9, 95% CI = 0.13-12.7). Conclusion: The p53 Pro72 allele was more frequent in Iranian POAG patients than in the control group (P<0.05). The present findings show that the individuals with the Pro/Pro genotype may be more likely to develop POAG. However, additional studies are necessary to confirm this association. Key Words: Primary open-angle glaucoma (POAG), Glaucoma, p53, Codon 72, Iran  相似文献   

13.
Background:Gastric cancer is the fourth most common human malignancy and the second reason for cancer morbidity worldwide. LncRNA HOTAIR has recently emerged as a promoter of metastasis in various cancer types, including GC, through the EMT process. However, the exact mechanism of HOTAIR in promoting EMT is unknown. Aberrant expression of the miR-200 family has been linked to the occurrence and development of various types of malignant tumors. This study investigates the correlation between the HOTAIR and miR-200 family gene expression patterns in GC cell lines. We investigated the miR-200 and HOTAIR due to their common molecular features in the EMT process. Methods:AGS and MKN45 cell lines were transfected with si-HOTAIR, along with a negative control. The effect of HOTAIR knockdown was also analyzed on cell viability and also on the expression of miR-200 family members, including miR-200a, -200b, and -200c, in cell lines using qRT-PCR. Statistical analysis was performed to find the potential correlation between the expression level of HOTAIR and miRs. Results:Our results showed significant increased miR-200 family expression level in transfected AGS and MKN45 GC cells (fold changes > 2; p < 0.001). Moreover, a negative correlation was observed between HOTAIR and miR-200 expression levels in GC cell lines (p < 0.05). Conclusion:Our findings showed a significant association between miR-200 family and HOTAIR expression levels in GC cell lines. Taken together, the HOTAIR-miR-200 axis seems to play a vital role in human GC, suggesting a potential therapeutic target in future GC treatment. Key Words: Gene expression, Long noncoding RNA, HOTAIR, MicroRNAs  相似文献   

14.
Background:The significance of cTfh cells and their subsets in atherosclerosis is not well understood. We measured the frequency of cTfh subsets in patients with different degrees of stenosis using flow-cytometry. Methods:Participants included high (≥50%; n = 12) and low (<50%; n = 12) stenosis groups, as well as healthy controls (n = 6). Results: The frequency of CCR7loPD-1hiefficient-cTfh was significantly higher in patients with high stenosis compared to healthy controls (p = 0.003) and correlated with LDL (p = 0.043), cholesterol (p = 0.043), triglyceride (p = 0.019), neutrophil count (p = 0.032), platelet count (p = 0.024), NLR (p = 0.046), and PLR (p = 0.025) in high stenosis group. The frequency of CCR7hiPD-1lo quiescent-cTfh was higher in healthy controls compared to the high-stenosis group (p = 0.001) and positively correlated with HDL (p = 0.046). The frequency of efficient-cTfh cells was correlated with platelet count (p = 0.043), NLR (p = 0.036), and PLR (p P = 0.035) in low-stenosis group, while that of quiescent-cTfh cells was negatively correlated with LDL (p = 0.034), cholesterol (p = 0.047), platelet count (p = 0.032), and PLR (p = 0.041). Conclusion:High percentages of cTfh and efficient-cTfh cells in patients with advanced atherosclerosis and their correlation with dyslipidemia and WBC counts suggests an ongoing cTfh subset deviation, towards efficient phenotype in the milieu of inflammation and altered lipid profile. Efficient cTfh cells have an effector phenotype and could in turn contribute to atherosclerosis progression. Key Words: Atherosclerosis, Blood Platelets, Neutrophils, Dyslipidemias  相似文献   

15.
Introduction:Lung injury is common in COVID-19 patients. The severity of lung injury appears to be reflected in serum KL-6, a glycoprotein expressed on type II alveolar epithelium. This study aims to assess the role of serum KL-6 in reflecting the severity of lung injury in COVID-19 patients. Methods:A systematic search was conducted in Scopus, PubMed, Wiley Online Library, and ProQuest. Articles were screened based on several eligibility criteria and assessed for study quality using NOS. Results:This systematic review included four studies involving a total of 151 adult COVID-19 patients. Pooled analysis revealed that serum KL-6 was significantly higher in severe patients (SMD = 1.16; 95% CI = 0.69–1.63) with moderately high pooled sensitivity (79%; 95% CI = 61–91%) and specificity (86%; 95% CI = 72–95%). Conclusion:High serum KL-6 may depict more severe lung injury in COVID-19 patients with moderately high sensitivity and specificity. Key Words: Biomarker, COVID-19, Infectious disease, Krebs von den Lungen-6, Lung injury  相似文献   

16.
Background:Glioblastoma multiforme is the most invasive and lethal form of brain cancer with unclear etiology. Our study aimed to investigate the molecular prevalence of HCMV and EBV infections in patients with GBM. Methods:This case-control study was conducted on 42 FFPE brain tumor samples from GBM patients and 42 brain autopsies from subjects without neurological disorders. The presence of EBV and HCMV DNA was determined, using PCR and nested-PCR assays, respectively. Results:HCMV DNA was detected in 3 out of 42 (7.1%) of GBM samples and was absent from the control group (p = 0.07). Importantly, EBV DNA was detected in 9 out of 42 (21.4%) brain tissue specimens of GBM subjects, but again in none of the control group (p = 0.001). Conclusion:Our findings indicate that infection with EBV is associated with GBM. Key Words: Brain tumor, Epstein-Barr virus, Glioblastoma, Human cytomegalovirus  相似文献   

17.
Background: The protein of Niemann-pick type C1 (NPC1) gene promotes the egress of cholesterol from late endosomes and lysosomes to other cellular compartments and contributes to a process known as reverse cholesterol transport. This study aimed to examine whether promoter methylation of NPC1 is associated with risk of cardiovascular disease (CVD). Methods: Fifty CVD patients and 50 healthy subjects as the control group were recruited in this study. Promoter methylation of NPC1 gene was defined using a nested-methylation specific polymerase chain reaction method. Statistical analyses were done using the chi-square, t-test or ANOVA tests. Results: Our study showed that the frequency of semi-methylated promoter (methylated/unmethylated status) was significantly higher in CVD patients than that in controls (OR = 6.521, 95% CI = 2.211-19.215, P = 0.008). However, a completely methylated promoter (methylated/methylated status) was not detected in any subjects in either of the two groups tested. Additionally, the analysis of clinical data according to the methylation status of NPC1 gene demonstrated that serum levels of total cholesterol, total triglycerides, high low-density lipoprotein cholesterol (LDL-C) and low high-density lipoprotein cholesterol (HDL-C) are influenced by NPC1 methylation, so that subjects with a completely unmethylated promoter (Unmethylated/unmethylated status) held lower levels of total triglycerides, total cholesterol, LDL-C and higher levels of HDL-C. Conclusion: Our findings propose that the NPC1 promoter methylation is a probable mechanism that can result in reduced/impaired NPC1 expression/activity and may thus contribute to progression of CVD. Key Words: Niemann-pick type C1 (NPC1), Promoter methylation, cardiovascular disease  相似文献   

18.
Background:To study the anticancer activity of Plantago major, we assessed the effect of ethanolic, methanolic and acetonic extracts of this plant on HCT-116, SW-480, and HEK-293 cell lines as control. Methods:The cytotoxic activity, biocompatibility, and toxicity were evaluated by MTT assay, hemolysis, and Artemia salina-LD50 (on mice) tests, respectively. The analysis of the extracts was performed by GC-MS analysis. Results:The results showed that all the extracts had the most antiproliferative properties on the HCT-116 cell line. The P. major root extract was more effective than the aerial parts, and IC50 values for ethanolic, methanolic and acetonic root extracts were 405.59, 470.16, and 82.26 µg/mL, respectively on HCT-116 cell line at 72 h. Hemolysis degree of the ethanolic extract of aerial and root parts were approximately 1% at 400 μg/mL.. Using the ethanolic extracts, the Artemia survived every concentration, and no toxicity was observed. One week after the oral administration of different parts of P. major extracts, none of the mice died, even those were administered 2000 mg/kg. The results of GC/MS analysis showed that P. major extracts contain potential anticancer compounds, such as stearic acid (8.61%) in aerial parts of methanolic extract and 1,2- Benzenedicarboxylic acid, mono(2-ethylhexyl)ester (88.07% and 40.63%) in aerial and root parts of acetonic extract of P. major. Conclusions:Our findings suggest that the P. major is a source of potential compounds with antiproliferative properties. Key Words: Gas chromatography-mass spectrometry, HCT-116 cells, Hemolysis, Lethal dose 50  相似文献   

19.
Background:This study was devoted to assessing the inhibitory potential of acetone, methanol, and ethanol extracts of Acroptilon repens against disease-associated enzymes, as well as their antioxidant/antibacterial activity and phytochemical composition. Methods:Comparative assessment using various antioxidant evaluation methods, including FRAP, scavenging ability on DPPH radical and hydrogen peroxide, and RP, indicated that the acetone extract presented the highest antioxidant activity, due to its highest total antioxidant content. Results:The TPC and TFC of these extracts were 3.44 ± 0.32 mg GAE/g DW and 2.09 ± 0.2 mg QE/g DW, respectively. The hydrodistillation essential oil from A. repens was analyzed by GC/MS, and 17 compounds were identified. All extracts showed good inhibitory activities against disease-related enzyme acetylcholinesterase and α-amylase, with the lowest IC50 for acetonic extract. Extracts of A. repens exhibited inhibiting activities against the Gram-positive bacteria, with the most effect of acetone extract. Conclusion:Our findings suggest A. repens as a promising source of natural antioxidant, antimicrobial, anti-cholinesterase and anti-amylase agents for the management of oxidative damage, and pharmaceutical, food, and cosmeceutical purposes. Key Words: Acroptilon repens, Antioxidants, Phytochemicals  相似文献   

20.
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